Abstract

AbstractPhotocatalytic semiconductor‐based nanoreactors, that convert nontoxic molecules into toxic ones for cancer therapy, have attracted great interest. However, its therapeutic efficiency is limited by the fast electron–hole recombination within a narrow bandgap, low oxidative damage of H2O2, and tumor hypoxia. Herein, aggregation‐limited hemin is introduced onto Bi2Se3 nanoparticles for successively solving these problems. The nanoreactor (Bi2Se3@hemin‐(G‐H)‐HA NPs) is obtained through adamantane modified hemin and β‐cyclodextrin modified hyaluronic acid complexing and wrapping on Bi2Se3 NPs via host–guest and electrostatic interaction. Once irradiated by NIR light, the hemin assists Bi2Se3 to separate electron–hole pairs and catalyze endogenous H2O to generate vast H2O2, resulting in a 3.9‐fold higher H2O2 generation than that of individual Bi2Se3. Subsequently, H2O2 is catalyzed by aggregation‐limited hemin to generate highly toxic •OH and •O2−, which improves the total reactive oxygen species generation of Bi2Se3@hemin‐(G‐H)‐HA by 10.8‐fold compared to that of Bi2Se3 NPs. Importantly, the cytotoxicity result exhibits a death rate of HepG2 cells of above 90%, even though in a simulated hypoxic environment. Additionally, the in vivo result indicates this nanoreactor realizes an synergetic anticancer effect with a tumor inhibition rate of 92.3%. Overall, such a nanoreactor with hemin‐assisted cascade catalysis is a promising candidate for improving therapeutic efficacy.

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